This study investigated effects of triterpenoids derived from Ganoderma lucidum (GLT) on the ability to attenuate cognitive impairment and reduce oxidative stress and inflammation induced by D-galactose using an aged rats model. The data revealed that dietary GLT intervention improved the memory of aged rats in a water maze experiment. A reduction in inflammation was also achieved as GLT decreased the levels of MDA, AGEs, NO, TNF-α and AChE activity, and increased the activity of T-AOC, GSH-Px, T-SOD, CAT and IL-2 level in serum. The GLT intervention revised hepatocyte cellular arrangement and binucleation of the liver status, and even hippocampal neurons morphology. GLT upregulated the expression of FOXO4, SIRT1, and downregulated the expression of GFAP, iNOS, PI3K, AKT, mTOR and IL-6 with activation of PI3K/AKT/mTOR pathway. The current study highlights a promising dietary approach for prevention or alleviation of oxidative stress, inflammation and cognitive impairment induced by age-related conditions.